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Sundowning: severe dementia and bringing on the night (melatonin and circadian angle)

John H. johnh at faraway.xxx
Sun Mar 30 02:55:05 EST 2003

Bright light therapy did not seem beneficial, excepts perhaps if provided in
afternoon. Melatonin appears to the treatment of choice and does help; more
research needed. The benefit may be related to sleep stabilisation thereby
limiting latter day fatigue. Don't know. Melatonin is a strong anti-oxidant,
that may be another factor involved here. The abstracts below do not provide
answers as to the exact cause of the agitation, however when we all get
sleepy we do get cranky ... . The violence issue interests me, Jane was
close to serious assault last week, managed to get through the security door
just before this lumbering hulk of man laid his hands on her. Hmmm, one
feels like picking up a baseball bat ... . How frustrating this must be for
those caring for such people.

Two drugs may benefit: Risperidone , donepezil, but I have no idea what they
are and what they do.

John H.

30/03/03 5:25pm

Neuroendocrinol Lett 2002 Apr;23 Suppl 1:20-3Related Articles,
=pubmed_pubmed&from_uid=12019347) Links

The use of melatonin in Alzheimer's disease.

Cardinali DP, Brusco LI, Liberczuk C, Furio AM.

Departament of Physiology, Faculty of Medicine, University of Buenos Aires,
Argentina. cardinal at mail.retina.ar

About 45% of Alzheimer's disease (AD) patients have disruptions in their
sleep and sundowning agitation. Since melatonin secretion is greatly
inhibited in AD patients we have used melatonin to treat sleep disorders in
AD patients since 1995. In a first study [21] we reported, in 7 out of 10
dementia patients treated with melatonin (3 mg p.o. at bed time), a
decreased sundowning. In a second study [22] we examined 14 AD patients who
received 9 mg melatonin daily for 22 to 35 months, observing a significant
improvement of sleep quality with stabilization of behavioral and cognitive
parameters. In a third study [23] we reported two monozygotic twins with AD
and similar cognitive impairment, one of them receiving 6 mg melatonin at
bedtime daily for 3 years. Melatonin treatment improved sleep quality and
suppressed sundowning. We now report the effect of melatonin (4-month-long
treatment with 6 mg/day) in 45 AD patients with sleep disturbances.
Melatonin improved sleep and suppressed sundowning, an effect seen
regardless of the concomitant medication employed to treat cognitive or
behavioral signs of AD. Melatonin treatment seems to constitute a selection
therapy to ameliorate sundowning and to slow evolution of cognitive
impairment in AD patients.

30/03/03 5:26pm

Am J Psychiatry 2001 May;158(5):704-11Related Articles,
Sundowning and circadian rhythms in Alzheimer's disease.

Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A.

Geriatric Research Education Clinical Center, Edith Nourse Rogers Memorial
Veterans Hospital, MA, USA.

OBJECTIVE: The goal of this study was to determine changes of circadian
rhythms induced by Alzheimer's disease and to explore relationships among
rhythm disturbances, sundowning, and sleep disturbances in patients with
Alzheimer's disease. "Sundowning" is the occurrence or exacerbation of
behavioral symptoms of Alzheimer's disease in the afternoon and evening.
METHOD: Circadian rhythms of core body temperature and motor activity were
measured in 25 patients with diagnoses of probable Alzheimer's disease and
in nine healthy individuals. The subjects with Alzheimer's disease were
divided according to the occurrence of sundowning as determined by staff
reports. RESULTS: The subjects with Alzheimer's disease had less diurnal
motor activity, a higher percentage of nocturnal activity, lower interdaily
stability of motor activity, and a later activity acrophase (time of peak)
than did the healthy individuals. They also had a higher mesor (fitted mean)
temperature, higher amplitude of the fitted cosine temperature curve, and
later temperature acrophase than did the healthy subjects. The severity of
sundowning was associated with later acrophase of temperature, less
correlation of circadian temperature rhythm with a 24-hour cycle, and lower
amplitude of temperature curve. CONCLUSIONS: These data indicate that
Alzheimer's disease causes disturbances of circadian rhythms and that
sundowning is related to a phase delay of body temperature caused by
Alzheimer's disease.

PMID: 11329390 [PubMed - indexed for MEDLINE]

30/03/03 5:27pm

Int J Geriatr Psychiatry 2000 Dec;15(12):1147-51Related Articles,
Improvement in sundowning in dementia with Lewy bodies after treatment with

Skjerve A, Nygaard HA.

Olaviken Behandlingssenter, 5306 Erdal, Bergen, Norway.
arvid,skjerve at hordaland-f.kommune.no

Sundowning, manifested as a recurring increase in restlessness and agitation
in the evening, is described in a 71-year-old man with clinically diagnosed
dementia with Lewy bodies. An objective measure of activity using the
activity electronic monitoring technique indicated a marked increase in
activity level during the evening compared to earlier in the day. After
treatment with donepezil, a cholinesterase inhibitor, ratings of behavioural
symptoms improved. In addition, there was a marked reduction in evening
activity and an increase in daytime activity. Cognition and parkinsonism
also improved. Possible explanations for this finding are discussed.
Copyright 2000 John Wiley & Sons, Ltd.

PMID: 11180473 [PubMed - indexed for MEDLINE]
30/03/03 5:27pm

Arch Gerontol Geriatr 2000 Aug 1;31(1):65-76Related Articles, Melatonin for
treatment of sundowning in elderly persons with dementia - a preliminary

Cohen-Mansfield J, Garfinkel D, Lipson S.

Society for the Inhibition of Age-Related Processes, Research Institute,
Hebrew Home of Greater Washington, 6121 Montrose Road, MD 20852, Rockville,

This pilot study investigated the impact of melatonin administration as a
clinical intervention for improving sleep and alleviating sundowning in 11
elderly nursing home residents who suffer from dementia. Melatonin is a
hormone produced and secreted by the pineal gland in response to darkness,
which plays a major role in the induction and regulation of sleep. Melatonin
production decreases with age. Age-related sleep disorders are frequently
associated with disruption of circadian cycle rhythms, and sometimes with
'sundowning'. Sundowning refers to the manifestation of agitation and/or
confusion in the evening hours. Agitation has been linked to sleep
disorders. Analysis revealed a significant decrease in agitated behaviors in
all three shifts, and a significant decrease in daytime sleepiness. There
was a nonsignificant decrease in latency (time to fall asleep) during the
evening shift and no significant changes were reported in night-time sleep
ratings. The results of this study are important, because finding ways of
decreasing sundowning in elderly persons may improve their well being,
alleviate the burden of the caregivers, and even enable caregiving in a less
restrictive environment.

PMID: 10989165 [PubMed - as supplied by publisher]
30/03/03 5:28pm

Chronobiol Int 2000 May;17(3):405-18Related Articles,
Circadian rhythms of agitation in institutionalized patients with
Alzheimer's disease.

Martin J, Marler M, Shochat T, Ancoli-Israel S.

San Diego State University/University of California, San Diego Joint
Doctoral Program in Clinical Psychology, USA.

Agitation is a common problem in institutionalized patients with Alzheimer's
disease (AD). "Sundowning," or agitation that occurs primarily in the
evening, is estimated to occur in 10-25% of nursing home patients. The
current study examined circadian patterns of agitation in 85 patients with
AD living in nursing homes in the San Diego, California, area. Agitation was
assessed using behavioral ratings collected every 15 minutes over 3 days,
and activity and light exposure data were collected continuously using
Actillume recorders. A five-parameter extension of the traditional cosine
function was used to describe the circadian rhythms. The mean acrophase for
agitation was 14:38, although there was considerable variability in the
agitation rhythms displayed by the patients. Agitation rhythms were more
robust than activity rhythms. Surprisingly, only 2 patients (2.4%) were
"sundowners." In general, patients were exposed to very low levels of
illumination, with higher illumination during the night being associated
with less robust agitation rhythms with higher rhythm minima (i.e., some
agitation present throughout the day and night). Seasonality was examined;
however, there were no consistent seasonal patterns found. This is the
largest study to date to examine agitation rhythms using behavioral
observations over multiple 24 h periods. The results suggest that, although
sundowning is uncommon, agitation appears to have a strong circadian
component in most patients that is related to light exposure, sleep, and
medication use. Further research into the understanding of agitation rhythms
is needed to examine the potential effects of interventions targeting sleep
and circadian rhythms.

PMID: 10841213 [PubMed - indexed for MEDLINE]

30/03/03 5:33pm

Am J Psychiatry 1992 Aug;149(8):1028-32Related Articles,
Bright light treatment of behavioral and sleep disturbances in patients with
Alzheimer's disease.

Satlin A, Volicer L, Ross V, Herz L, Campbell S.

Department of Psychiatry, Harvard Medical School, Belmont, Mass.

OBJECTIVE: The authors tested the hypothesis that evening bright light
pulses would improve sleep-wake patterns and reduce agitation in patients
with Alzheimer's disease who have severe sundowning (a syndrome of recurring
confusion and increased agitation in the late afternoon or early evening)
and sleep disorders. METHOD: Ten inpatients with Alzheimer's disease on a
research ward of a veterans' hospital were studied in an open clinical
trial. All patients had sundowning behavior and sleep disturbances. After a
week of baseline measurements, patients received 2 hours/day of exposure to
bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline
week, the treatment week, and a posttreatment week, patients were rated by
nurses for agitation, sleep-wake patterns, use of restraints, and use of
prescribed-as-needed medication. On the last 2 days of each week, patients
wore activity monitors. Activity counts were analyzed for circadian
rhythmicity. RESULTS: Clinical ratings of sleep-wakefulness on the evening
nursing shift improved with light treatment in eight of the 10 patients. The
proportion of total daily activity occurring during the nighttime decreased
during the light-treatment week. The relative amplitude of the circadian
locomotor activity rhythm, a measure of its stability, increased during the
light-treatment week. More severe sundowning at baseline predicted greater
clinical improvement. CONCLUSIONS: Evening bright light pulses may
ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's
disease. This effect may be mediated through a chronobiological mechanism.

PMID: 1353313 [PubMed - indexed for MEDLINE]

30/03/03 5:41pm

Am J Health Syst Pharm 2000 May 1;57(9):862-70Related Articles,
Risperidone for control of agitation in dementia patients.

Falsetti AE.

Division of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy
and Health Sciences, Long Island University, Brooklyn, NY 11201-5497, USA.

Currently available research on the use of risperidone to manage agitation
in patients with dementia is discussed. Dementia affects up to 70% of
nursing-home patients, and more than 90% of them exhibit aggressive or
agitated behavior or severe depression. Agitation includes combativeness,
hyperactivity, disinhibition, wandering, and restlessness. Environmental
interventions are preferred for mild symptoms; medications are the treatment
of choice for severe manifestations. Traditional neuroleptics have been the
mainstay of treatment for agitated behavior in persons with dementia, but
these agents have limited efficacy and are associated with high rates of
adverse effects, including worsening of already poor cognitive functioning.
Although the literature on the use of risperidone in elderly patients with
dementia consists largely of uncontrolled trials, case reports, and chart
reviews, it appears that this agent is effective for managing agitation in
this population and does so with a low frequency of extrapyramidal symptoms
(EPS). Risperidone may also be useful for treating acute agitation in
patients with a high risk of EPS and for long-term treatment of "sundowning"
(agitation and confusion starting in the late afternoon and worsening at
night). A low initial dosage that is gradually adjusted upward is
recommended. Risperidone appears effective in controlling agitation in
patients with dementia and has a relatively benign adverse-effect profile,
but more clinical trials are needed to elucidate its role for this

Publication Types:
· Review
· Review, Tutorial

PMID: 10840527 [PubMed - indexed for MEDLINE]
30/03/03 5:39pm

Z Gerontol Geriatr 2001 Dec;34(6):491-7Related Articles,
=pubmed_pubmed&from_uid=11828891) Links

Melatonin in elderly patients with insomnia. A systematic review.

Olde Rikkert MG, Rigaud AS.

Dept. Geriatric Medicine, University Hospital Nijmegen, Code 318, PO Box
9101, 6500 HB Nijmegen, The Netherlands. M.Olde-Rikkert at czzoger.azn.nl

BACKGROUND: Melatonin is a hormone and antioxidant produced by the pineal
gland of which four neurobiological roles have been claimed in the aged
population: anti-ageing agent; free-radical scavenger; regulator of
circadian rhythm; endogeneous sleep-inducer. The "melatonin replacement"
hypothesis states that 1) the well-evidenced age-related decline contributes
to insomnia and that 2) replacement with physiological doses of melatonin
improves sleep. The aim of this review was to determine the evidence for the
efficacy of melatonin in elderly insomniacs. METHODS: MEDLINE's database
from 1990-2000 was searched with "melatonin", "geriatrics" and
"(frail)-elderly" as major sub-headings. This resulted in 78 articles: only
studies with empirical treatment data were reviewed (N = 12). RESULTS: Six
reports (abstract, research letter, retrospective case study, 3 open label
studies) showed a trend towards efficacy of melatonin: sleep quality
improved and in patients with Alzheimer's disease sundowning was reduced. In
6 double blind, randomised crossover trials, a total number of 95 patients
(mean ages: 65-79 yrs) were treated. Melatonin doses ranged from 0.5 mg to 6
mg; most took a single dose 30-120 min before bedtime. In 3 studies a slow
release form was used. Sleep quality was objectively measured by wrist
actigraphy (n = 4) and polysomnography (n = 2), and additionally subjective
sleep quality was assessed (n = 2). Sleep latency decreased significantly in
4 studies. In 3 studies other measures of sleep quality (sleep efficiency,
total sleep time and wake time during sleep) improved. Subjective sleep
quality did not improve. No early-morning sleepiness occurred. Comparison of
the studies suggests that melatonin is most effective in elderly insomniacs
who chronically use benzodiazepines and/or with documented low melatonin
levels during sleep. CONCLUSION: There is sufficient evidence that low doses
of melatonin improve initial sleep quality in selected elderly insomniacs.
However, larger randomized controlled trials, with less strict inclusion
criteria are necessary to yield evidence of effectiveness (i.e. clinical and
subjective relevance) in geriatric patients who suffer from insomnia, before
wide-spread use can be advocated.

Publication Types:
· Review
· Review Literature

PMID: 11828891 [PubMed - indexed for MEDLINE]

Publication Types:
· Review
· Review, Tutorial

PMID: 12019347 [PubMed - indexed for MEDLINE]

"John H." <johnh at faraway.xxx> wrote in message
news:OXiha.256$1h6.12035 at nnrp1.ozemail.com.au...
> The story on vitamin D deficiency. Somewhat alarmist but important to
> This is from the excellent science program in Aus: Catalyst. We seem to be
> good at that.
> John H.
> http://www.abc.net.au/catalyst/stories/s805444.htm
> "John H." <johnh at faraway.xxx> wrote in message
> news:4niha.255$1h6.12990 at nnrp1.ozemail.com.au...
> > Particularly significant given the Out of Africa Theory currently in
> > and well substantiated by paleanthropological, linguistic and genetic
> data.
> > Emerging from sunny Southern Africa approx 120,000 years ago, it is
> > estimated we were in Europe by circa 60,000 years ago. Thus our diurnal
> > variations may be more attuned to that previous sunny climate and subtle
> > variations ensue ... .
> >
> > John H.
> > "Wayne Alan Simon" <ariess at bellsouth.net> wrote in message
> > news:lSbha.71399$d15.34079 at fe06.atl2.webusenet.com...
> > > Many biological systems are effected by daylight or lack thereof.
> > are
> > > turned on and off via the light. Some are increased or decreased from
> > light
> > > ( various sources and wavelengths).  Evolving on a planet that for the
> > most
> > > part has day and night cycles, has also allowed for various
> or
> > > maladaptions based on the planets light darkness cycle. Of course if
> > > live in an area that is light half the year and dark half the year,
> > may
> > > find your biological systems adapted quite differently.  Diurnal
> > variations
> > > in most neurohormonal and endocrine systems is the rule and not the
> > > exception.  Vitamin D, as mentioned many times is just one factor of
> many.
> > > The situation is complex, and to shed a little "light" on the subject
> > > always enlightening!
> > >
> > >
> > >
> >
> >

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